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We agree that genetic studies have so far explained only a small
fraction of the heritability of ALS (1,2), and this is true in many other
diseases as well (3). Epigenetic factors are almost certainly part of the
answer, but there are also several other possibilities. We are only just
developing the tools to look for disease-associated rare variants on a
large scale. In addition, we do not understa...
We agree that genetic studies have so far explained only a small
fraction of the heritability of ALS (1,2), and this is true in many other
diseases as well (3). Epigenetic factors are almost certainly part of the
answer, but there are also several other possibilities. We are only just
developing the tools to look for disease-associated rare variants on a
large scale. In addition, we do not understand the genetic code for most
of the genome since we can only reliably translate the 1% that is exonic
sequence (4). This means much variation cannot be interpreted even though
it is very likely to contribute to disease and the associated genetic
variants may be weak correlates of the larger effect true causal variant.
We do not routinely search for interaction between genes or genes and
environment and there is no easy method to interpret the actions of
multiple gene variants acting in concert. Furthermore, the three
dimensional nature of the genome is not considered but may have a role to
play in disease if variants in physical proximity interact through protein
binding or other mechanisms.
As genetic, statistical and computing technologies advance, we expect
our current linear and simple view of the genome to be transformed and far
more of the so-called missing heritability explained.
(1) Al-Chalabi A, Fang F, Leigh PN, et al. An estimate of
amytotrophic lateral sclerosis heritability using twin data. J Neurol
Neurosurg Psychiatry 2010;81:1324-1326
(2) Shatunov A, Mok K, Newhouse S, et al. Chromosome 9p21 in sporadic
amyotrophic lateral sclerosis in the UK and seven other countries: a
genome-wide association study. Lancet Neurol 2010;9,986-994
(3) Manolio TA, Collins FS, Cox NJ, et al. Finding the missing
heritability of complex diseases. Nature 2009;461,747-753
(4) Taft RJ, Pheasant M, and Mattick JS. The relationship between non
-protein-coding DNA and eukaryotic complexity. Bioessays 2007;29:288-299
The twin studies show conclusively the limits of classical genetics
in the studies of the etiology and pathogenesis of the ALS (1).
It has been suggested that a susceptibility or familial factor could
play a role. In this case, they may be mediated by epigenetic mechanisms
which control the activity and expression of the genome (2).
The incorrectly coded polypeptides could lead to...
The twin studies show conclusively the limits of classical genetics
in the studies of the etiology and pathogenesis of the ALS (1).
It has been suggested that a susceptibility or familial factor could
play a role. In this case, they may be mediated by epigenetic mechanisms
which control the activity and expression of the genome (2).
The incorrectly coded polypeptides could lead to a gain of function
of an enzyme or to aberrant tertiary structures of protein species (3).
This sequence of events could also shed light on familial cases as
family members often are exposed to similar environment or other exogenous
factors.
1 Al-Chalabi A, Fang F, Leigh PN, et al. An estimate of amytotrophic
lateral sclerosis heritability using twin data. J Neurol Neurosurg
Psychiatry 2010; 81: 1324-1326
2 Stauffer BL, DeSouza CA. Epigenetics: an emerging player in health
and disease. J appl Physiol 2010; 109: 230-231
3 Palo J, Savolainen H, Kivalo E. Comparison between the proteins of
human brain myelin in subacute sclerosing panencephalitis, amyotrophic
lateral sclerosis and malignant diseases. J neurol Sci 1973; 18: 175-181
The twin studies show conclusively the limits of classical genetics
in the studies of the etiology and pathogenesis of the ALS (1).
It has been suggested that a susceptibility or familial factor could
play a role. In this case, they may be mediated by epigenetic mechanisms
which control the activity and expression of the genome (2).
The incorrectly coded polypeptides could lead to...
The twin studies show conclusively the limits of classical genetics
in the studies of the etiology and pathogenesis of the ALS (1).
It has been suggested that a susceptibility or familial factor could
play a role. In this case, they may be mediated by epigenetic mechanisms
which control the activity and expression of the genome (2).
The incorrectly coded polypeptides could lead to a gain of function
of an enzyme or to aberrant tertiary structures of protein species (3).
This sequence of events could also shed light on familial cases as
family members often are exposed to similar environment or other exogenous
factors.
1 Al-Chalabi A, Fang F, Leigh PN, et al. An estimate of amytotrophic
lateral sclerosis heritability using twin data. J Neurol Neurosurg
Psychiatry 2010; 81: 1324-1326
2 Stauffer BL, DeSouza CA. Epigenetics: an emerging player in health
and disease. J appl Physiol 2010; 109: 230-231
3 Palo J, Savolainen H, Kivalo E. Comparison between the proteins of
human brain myelin in subacute sclerosing panencephalitis, amyotrophic
lateral sclerosis and malignant diseases. J neurol Sci 1973; 18: 175-181
The article 'Disorders of Visual Perception' (ffytche, Blom &
Catani, JNNP 2010;81:1280-1287) presents an interesting new classification
of disorders of visual perception. It describes a wide range of disorders
whose sources are cortical or subcortical rather than due to diseases of
the eye. Each is classified as a disorder of one brain region (topological
disorders) or of connectivity between re...
The article 'Disorders of Visual Perception' (ffytche, Blom &
Catani, JNNP 2010;81:1280-1287) presents an interesting new classification
of disorders of visual perception. It describes a wide range of disorders
whose sources are cortical or subcortical rather than due to diseases of
the eye. Each is classified as a disorder of one brain region (topological
disorders) or of connectivity between regions (hodological disorders); and
as reflecting a decrease (hypofunction) or increase (hyperfunction) in
function. The disorders are also divided by different types of visual
function, such as disorders of visual memory or visual attention. One of
few 'empty cells' in the framework is an example of a visual motor,
topological hyperfunction. On the basis of work from our laboratory and
others, we would like to argue that a good example for this cell is over-
reactions to visual information for locomotion in Parkinson's disease
(PD).
This topic came to our attention through the phenomenon of 'freezing'
in PD. A freeze occurs when a patient is unable to walk despite wanting to
do so: subjectively, the patient feels as if he is 'glued to the floor'.
Freezing has long been associated with unusual responses to visual
stimuli. In paradoxical kinesia, a freeze is unblocked, or short strides
lengthened, by vision of transverse lines on the floor (Azulay et al,
1999). Patients who freeze ('freezers') show large responses to visual
optic flow information in a balance task (Bronstein et al, 1990). We have
recently shown that these patients also slow down dramatically when
passing through doorways (Cowie et al, 2010). Whereas healthy controls
slowed to a degree inversely proportional to door width (allowing accurate
passage), freezers did so to a dramatic extent. Each visually specified
change in door width elicited a larger drop in velocity for PD freezers
than for healthy controls. The patients had no difficulties in explicitly
judging the width of door, and the extent of slowing was not predicted by
simpler motor abilities such as turning. Rather, the result indicates that
responses to action-relevant visual information about door width were
exaggerated in this group. This theory resolves the apparent paradox that
visual information can help or hinder walking depending on the
circumstance. Current evidence suggests that these effects are specific to
freezers, since other patients with PD are not susceptible to such effects
(Almeida & Lebold, 2010).
From these results showing over-responses to visual information, we
can argue that our visual motor disorder is one of hyperfunction. What of
its neural basis? Visual control of action activates a network of brain
areas including the dorsal stream, premotor cortices and cerebellum.
However, a SPECT study (Hanakawa et al, 1999) suggests that one specific
area is involved in hypersensitive locomotor responses to visual
information. In this study freezers and non-freezers walked on a treadmill
with lines painted parallel or transverse to the direction of walking. As
expected, the PD group had exaggerated responses to transverse lines, a
form of 'paradoxical kinesia'. When comparing the brain response to
transverse and parallel lines, only the right lateral premotor cortex
(PMC) was more active in PD patients than in controls. Thus this area
seems to be the focus of the over-reaction to action-relevant visual
information in walking in PD freezers. Within ffytche et al's framework we
would therefore classify over-reactions to visual information for
locomotion in Parkinson's disease (PD) as a topological disorder of
hyperfunction, specifically of the lateral premotor cortex.
Of course this classification is subject to the same limitations that
the authors acknowledge in their article. Though the behaviour we measure
is a 'hyperfunction', it coexists with other disease symptoms which are
certainly 'deficits' in ffytche et al's terms. The primary disturbance in
PD is the dopaminergic deficit in the striatum. Though there is little
literature on the subject, a possibility is that over-reactions to visual
information (and indeed freezing of gait) in PD are a direct result of
this deficit. This would mean PMC hyperfunction is a downstream result of
a basal ganglia deficit. Clearly, this makes the classification scheme
more ambiguous than it first appears. Furthermore, though Hanakawa et al's
study shows one clear focus of overactivation, this may result from damage
to networks of areas including connections between the PMC and its sensory
input areas or motor output areas.
Nevertheless, a clear strength of ffytche et al's framework is that
novel disorders can be brought within its structure. This allows
consideration of the novel disorder within a broader context at the same
time as fleshing out the model. We argue that visual control of locomotion
in Parkinson's disease (PD) can be considered this way, and look forward
to further discussions surrounding the framework and its contents.
Yours sincerely
Dr Dorothy Cowie, Goldsmiths, University of London
Prof Brian L Day, UCL Institute of Neurology
References
Azulay, J., Mesure, S., Amblard, B., Blin, O., Sangla, I.,&
Pouget, J. (1999). Visual control of locomotion in Parkinson's disease.
Brain, 122, 111-20.
Bronstein, A. M., Hood, J. D., Gresty, M. A., & Panagi, C.
(1990). Visual control of balance in cerebellar and Parkinsonian
syndromes. Brain, 113, 767-79.
Cowie D, Limousin P, Peters A, & Day BL. (2010). Insights into
the neural control of locomotion from walking through doorways in
Parkinson's disease. Neuropsychologia, 48, 2750-57.
Almeida QJ, & Lebold CA. (2010). Freezing of gait in Parkinson's
disease: a perceptual cause for a motor impairment? J Neurol Neurosurg
Psychiatry, 81, 513-18.
Hanakawa T, Fukuyama H, Katsumi Y, Honda M, & Shibasaki H.
(1999). Enhanced lateral premotor activity during paradoxical gait in
Parkinson's Disease. Ann Neurol, 45, 329-36.
Recent developments by Harloff ( 2008 ) describibg high risk plaques
detected by TOE and MRI in aortic arch , and cryptogenic stroke , depicted
certain characteristics ( > 4 mm thickness or presence of ulcerations
or mobile components ) . Considering associated conditions , such aortic
thrombi are defined as laminated deposition along the initial surface
with variable echogenicity with or without mobile lesions...
Tou...
Recent developments by Harloff ( 2008 ) describibg high risk plaques
detected by TOE and MRI in aortic arch , and cryptogenic stroke , depicted
certain characteristics ( > 4 mm thickness or presence of ulcerations
or mobile components ) . Considering associated conditions , such aortic
thrombi are defined as laminated deposition along the initial surface
with variable echogenicity with or without mobile lesions...
Touz? pinpointed the importance not only of plaque thickness , but the
relevance of coronary classifications : thin cap with a large lipid
necrotic core , active inflammation , fissured plaque and intraplaque
haemorrhages in ascending aorta and prximal arch
M.Tanaka Gutiez, L.Jarrett, B. Nevin, J. Stewart and S. Weatherby
Sir,
A recent study published in the JNNP suggests that quality of life for
people living with motor neuron disease (PwMND) is influenced by their
perceptions of social support[1].
We would like to share the results of a study carried out jointly
with the Motor Neurone Disease Association (MNDA) and the peninsula MND
network, which fu...
M.Tanaka Gutiez, L.Jarrett, B. Nevin, J. Stewart and S. Weatherby
Sir,
A recent study published in the JNNP suggests that quality of life for
people living with motor neuron disease (PwMND) is influenced by their
perceptions of social support[1].
We would like to share the results of a study carried out jointly
with the Motor Neurone Disease Association (MNDA) and the peninsula MND
network, which further highlights the importance of understanding the
experience and perceptions of PwMND.
Stakeholder involvement in service development is recognised as
important. Patients and care providers may have different perceptions
regarding care needs[2-5]. In designing our service we therefore
performed a joint study with the MNDA, to understand the attitudes,
perceptions and priorities of PwMND, neurologists and multidisciplinary
team (MDT) members.
PwMND across Devon and Cornwall (N=135) received a questionnaire
administered by the MNDA. The questions were based on an audit tool
prepared by the MNDA, Standards of Care to Achieve Quality of Life.
Questionnaires were also sent to all neurology consultants across Devon
and Cornwall (N=16), and to a representative sample of MDT teams in the
region (N=30). The questionnaires were divided into six subsections: 1)
presentation to diagnosis; 2) diagnosis; 3) post diagnosis; 4) MNDA
involvement; 5) interprofessional communication; and 6) overall service.
Each questionnaire had a free text section which respondents were
encouraged to complete. The response rates for the PwMND, neurologists and
MDT teams were 35.6% (48 of 135), 100% (16 of 16), and 70% (21 of 30),
respectively.
A number of issues were highlighted, revealing points of agreement
and difference between the perceptions of patients and care providers.
12 of the 16 neurologists (75%) felt that it was appropriate to give
PwMNDs information at diagnosis, however, only 25 of 48 (52.1%) PwMNDs
reported information being given and only 7 of 16 (43.8%) of MDT members
felt that PwMNDs were well informed. These results correspond with other
studies [2;3] . Furthermore, 30 of 48 (62.5%) PwMNDs in our study who
were given information would have liked more.
Despite a consensus amongst neurologists (13 of 16 neurologists
(81.3%)) that PwMND should be referred to the MNDA at diagnosis, only 14
of the 48 PwMNDs (29.2%) recalled being referred at that point.
Subsequently however, 43 out of 48 PwMND (89.6%) made contact with the
MNDA at some point of their disease trajectory and 35 (81.3 %) of these
people found it useful.
Neurologists and MDT members appeared to under appreciate the
importance which PwMND attach to their experience around the time of
diagnosis (19 of 32 of PwMND comments (59.4%), vs 1 of 13 (7%)
neurologists, vs 0% for MDT members).
When asked to indicate the areas of care most in need of improvement,
all groups identified a need to optimise care coordination and follow-up
care [12 of 32 comments (38%) for PwMND, 7 of 13 comments (54%) for
neurologists, and 8 of 13 comments (64%) for MDT members].
In order to offer patient-centred care it is necessary to understand
and appreciate the perceptions of the patient. This however can be
difficult, particularly for an uncommon condition such as motor neurone
disease (MND). Our findings demonstrate the value that PwMND attach to
input of the MNDA in their care.
They also highlight that perspectives can differ between care givers and
care receivers, and thus emphasise the importance of involving all
stakeholders in developing services. PwMND attach great importance to
issues surrounding their care at diagnosis, and this appeared to be
underestimated by care providers.
As a consequence of this study the MND Network care coordinator offers
PwMND a visit at home or in a clinical setting a few weeks post diagnosis.
To improve coordination of care, complex care pathways have been developed
and are put into action through regular multidisciplinary meetings in the
various regions of the Peninsula.
Competing Interest: None declared.
Licence for Publication:
The Corresponding Author has the right to grant on behalf of all authors
and does grant on behalf of all authors, an exclusive licence (or non
exclusive for government employees) on a worldwide basis to the BMJ
Publishing Group Ltd to permit this article (if accepted) to be published
in JNNP and any other BMJPGL products and sublicences such use and exploit
all subsidiary rights, as set out in our licence.
(http://group.bmj.com/products/journals/instructions-for-authors/licence-
forms)
Reference List
1. Matuz T, Birbaumer N, Hautzinger M, Kubler A. Coping with
amyotrophic lateral sclerosis: an integrative view. J Neurol Neurosurg
Psychiatry 2010;81:893-8.
3. Hancock K, Clayton JM, Parker SM, Wal dS, Butow PN, Carrick S,
Currow D, Ghersi D, Glare P, Hagerty R, Tattersall MH. Truth-telling in
discussing prognosis in advanced life-limiting illnesses: a systematic
review. Palliat Med 2007;21:507-17.
4. McCluskey L, Casarett D, Siderowf A. Breaking the news: a survey
of ALS PwMNDs and their caregivers. Amyotroph Lateral Scler Other Motor
Neuron Disord 2004;5:131-5.
5. McIlfatrick S. Assessing palliative care needs: views of PwMNDs,
informal carers and healthcare professionals. J Adv Nurs 2007;57:77-86.
I read the article by Weimar, et al with interest. The authors
describe the largest case series to date of cervico-cephalic dissection in
a multi-hospital registry in Germany. I found the findings on the risk of
recurrent stroke being lower in the anti-coagulation group, similar in
internal carotid versus vertebral artery, and higher in the occlusion
versus stenosis group telling. The overall risk of recurrent stroke bein...
I read the article by Weimar, et al with interest. The authors
describe the largest case series to date of cervico-cephalic dissection in
a multi-hospital registry in Germany. I found the findings on the risk of
recurrent stroke being lower in the anti-coagulation group, similar in
internal carotid versus vertebral artery, and higher in the occlusion
versus stenosis group telling. The overall risk of recurrent stroke being
high, particularly in the first year, was a useful result for clinical
care. As the authors pointed out they did not include patients with
asymptomatic dissection, but 12% of the sample did not have a cerebral
infarction and presumably had a TIA. Were the patients with no cerebral
infarction at a different risk of recurrence?
I wondered however if case selection may have driven some of the
results as I have encountered several cases that were erroneously
diagnosed with dissection. I have encountered several patients with
atherosclerotic plaque rupture with subsequent "dissection" that may
appear as a vessel wall hematoma. The selection of patients was a concern
as some may have had atherosclerosis rather than dissection.
Atherosclerosis could have a very different risk of recurrence than
dissection. The average age of the sample was 48, and the standard
deviation was 12 indicating that a substantial proportion of the sample
was aged 60 or older. In addition the burden of atherosclerotic disease
risk factors was high in the sample (40% had hypertension, 35% smoked)
while few had an indentified trigger for dissection (though this is common
in dissection case series). The most common diagnostic finding was long
segment stenosis, which could well be due to atherosclerosis rather than
dissection in many cases given that atherosclerosis is much more common
that dissection (1). Was the risk of recurrence different based on that
vascular finding? Further information on how vertebral dissection was
diagnosed would have been interesting given the difficulties with
diagnostic modalities in this artery, or the carotid artery (2, 3). Fat-
suppressed MRI may not be optimal, and not visualizing whether there are
calcifications in the artery may make vertebral dissection difficult to
diagnose. There was also little information on whether the patients were
imaged on follow up, and resolution of the abnormalities on imaging would
have been more telling.
There were 5 in hospital deaths, and 13 recurrent strokes, for which
it may have been useful to know if the deaths or recurrences were due to
ischemic or hemorrhagic stroke. In clinical rounds we often discuss the
risk of acute anti-coagulation in patients with vertebral dissection out
of concern that they may subsequently develop subarachnoid hemorrhage.
1 Dittrich R, Nassenstein I, Harms S, Maintz D, Heindel W,
Kuhlenb?umer G, Ringelstein EB. Arterial elongation ("redundancy") is not
a feature of spontaneous cervical artery dissection. J Neurol. 2010 Sep
10. [Epub ahead of print]
2 Khan S, Cloud GC, Kerry S, Markus HS. Imaging of vertebral artery
stenosis: a systematic review. J Neurol Neurosurg Psychiatry 2007;78:1218-
1225
3 Naggara O, Louillet F, Touz? E, Roy D, Leclerc X, Mas JL, Pruvo JP,
Meder JF, Oppenheim C. Added Value of High-Resolution MR Imaging in the
Diagnosis of Vertebral Artery Dissection. AJNR Am J Neuroradiol. 2010 Jul
1. [Epub ahead of print]
I read the article on disability progression in patients with
multiple sclerosis whether treated with interferon or not with interest(1)
Although may of the placebo treated patients probably were treated
with some form of immunomodulatory treatment after the study period, it
certainly raises the question of whether neuronal progression in multiple
sclerosis is due to accumulated deficits from exacerbations and re...
I read the article on disability progression in patients with
multiple sclerosis whether treated with interferon or not with interest(1)
Although may of the placebo treated patients probably were treated
with some form of immunomodulatory treatment after the study period, it
certainly raises the question of whether neuronal progression in multiple
sclerosis is due to accumulated deficits from exacerbations and remissions
or is related to an underlying progressive process.
Although relapsing-remitting, secondarily progressive and primary
progressive multiple sclerosis have been approached differently with
respect to treatment, the similar accumulated disability in the treated
vs. non-treated groups in the study would indicate accumulated deficit in
the different forms of multiple sclerosis may be the same.
Multiple sclerosis may primarily be a progressive disease of the CNS,
with development of immunity to CNS components due to exposure of CNS
components to the immune system from alteration of the blood brain
barrier.
The blood brain barrier is a neurovascular unit consisting of
cerebral microvascular endothelium, astrocytes, pericytes, neurons,
extracellular matrix. Tight junctions between endothelial cells of the
blood brain barrier restrict diffusion of perivascular diffusion of water-
soluble substances from blood to brain (2).
While the blood brain barrier has been considered primarily a barrier
to components of the circulatory system from leaking into the brain from
the circulation, the function of preventing CNS components from leaking
out of the CNS into the circulation may be even more important.
If CNS components leak into the peripheral circulation,
autoimmunization to components of the CNS would be expected to occur,
since usually the CNS is immunologically isolated from the traditional
immune system.
MS may be a disease triggered by breakdown of the neurovascular unit
of the blood-brain-barrier, leakage of CNS components into the peripheral
circulation, and subsequent development of autoimmunity to the CNS.
While interferon treatments may reduce exacerbations and remissions
from flare-ups of autoimmunity, the basic disease process may continue in
a smoldering fashion in the background, with development of progressive
disability.
References:
1. G C Ebers, A Traboulsee, D Li, D Langdon, A T Reder et al.
Analysis of clinical outcomes according to original treatment groups 16
years after the pivotal IFNB-1b trial. J Neurol Neurosurg Psychiatry 2010;
81: 907-912.
2. BT Hawkins, TP Davis. The blood-brain barrier/neurovascular unit
in health and disease. Pharmacol Rev. 2005; 57: 173-185.
Re: Spinal cord involvement in posterior reversible encephalopathy syndrome. B Lapuyade, I Sibon, S Jeanin, V Dousset jnnp 2009;80:35 doi:10.1136/jnnp.2008.154781
Dear Editor,
We read with great interest the article, "Spinal cord involvement in posterior reversible encephalopathy syndrome" published by B Lapuyade et al (JNNP January 2009). We recently treated a patient with similar presentation. She was 22 year old female who pre...
Re: Spinal cord involvement in posterior reversible encephalopathy syndrome. B Lapuyade, I Sibon, S Jeanin, V Dousset jnnp 2009;80:35 doi:10.1136/jnnp.2008.154781
Dear Editor,
We read with great interest the article, "Spinal cord involvement in posterior reversible encephalopathy syndrome" published by B Lapuyade et al (JNNP January 2009). We recently treated a patient with similar presentation. She was 22 year old female who presented with nausea, vomiting, headache, blurred vision and intermittent confusion. Her past medical history was notable for history of lupus induced acute proliferative glomerulonephritis when she was 13 years of age. Subsequently she had been maintained on plaquenil, azathioprine and low dose prednisone. At the time of admission her blood pressure was documented to be 247/150. She was encephalopathic, but moved all extremities equally. Her deep tendon reflexes were globally brisk with extensor planters bilaterally. Her serum creatinine was 6.1 mg/dl which was higher than her baseline of about 2.
MRI of head revealed hyperintense confluent lesion on T2WI which involved medulla, cerebellum and extended on to the cervical cord. Subsequent MRI of cervical and thoracic cord confirmed the lesion extending to the entire cord (figure 1A, 1B and 1C). Contrast was not administered since the patient had renal impairment. On spinal tap, her cerebrospinal fluid studies were normal, and serum NMO titers were negative. Based on her imaging abnormalities, negative CSF and NMO serology; she was diagnosed with posterior reversible encephalopathy syndrome (PRES). There was notable disparity between imaging studies and clinical examination, i.e., lack of weakness, which typically does not occur with myelitis.
Patient was treated aggressively with antihypertensive agents and hemodialysis. On renal biopsy she was found to have advanced sclerosing lupus nephritis for which she was given pulse steroids. She improved rapidly and a repeat MRI scan of cervical spine a week later revealed complete resolution of lesions (figure 1D).
There are now multiple reports showing involvement of spinal cord in PRES (1, 2, 3). MRI of spinal cord of our patient revealed confluent hyperintense T2WI lesion extending the entire length of the cord, extending to the brain stem and cerebellum, similar to the imaging studies in the case presented by Dr Lapuyade and his colleagues. The disparities of radiological abnormalities to clinical examination(4), resolution of lesions within one to two weeks were also common to both cases. As discussed in the article, the impairment of endothelial cells due to uncontrolled hypertension is considered to be the underlying Pathophysiology leading to vasogenic edema. Our hypothesis is that these factors also involve the spinal cord blood vessels.
Though the incidence of spinal cord involvement in PRES remains to be studied extensively, with more cases of PRES with spinal cord involvement being identified, it may well be time to consider changing the name from Posterior Reversible Encephalopathy syndrome (PRES) to Posterior Reversible Enchephalo-Myelopathy Syndrome (PREMS). Increased awareness of spinal cord involvement in this syndrome would help avoid misdiagnosis of these patients as having Transverse Myelitis.
References
1) Briganti C, Caulo M, Notturno F, Tartaro A, Uncini A. Asymptomatic spinal cord involvement in posterior reversible encephalopathy syndrome. Neurology 2009; 73:1507-1508.
2) Lapuyade B, Sibon I, Jeanin S, Dousset V. Neurological picture: spinal cord involvement in posterior reversible encephalopathy syndrome. J Neurol Neurosurg Psychiatry 2009; 80:35.
3) Milia A, Moller J, Pilia G, et al. Spinal cord involvement during hypertensive encephalopathy: clinical and radiological findings. J Neurol 2008; 255:142-143.
4) Cruz-Flores S, Gondim GAA, Leira EC. Brainstem involvement in hypertensive encephalopathy: clinical and radiological findings. Neurology. 2004; 62(8):1417-1419.
Figure legends - available upon request.
.Figure 1:
MRI brain T2 weighted (A) axial cut images showing hyperintensity within the medulla and right greater than left cerebellar hemispheres, (B) sagittal section, signal abnormality throughout the cervical spinal cord and extending superiorly to medulla, (C) axial cut, signal abnormality at cervical level with some expansion of the cord and (D) complete resolution of the signal abnormality seen on the prior scan, after 1 week of presentation.
Figures available upon request.
Moseley et al report an interesting case of Parry Romberg syndrome
with contralateral MRI changes. A similar case of Scleroderma 'en coup de
sabre' was published previously in JNNP. This case also had a brain biopsy
of a contralateral thalamic lesion and similar perivascular inflammatory
changes were seen [1].
Reports of neuropathology remain rare in these overlap conditions.
This additional report is useful in...
Moseley et al report an interesting case of Parry Romberg syndrome
with contralateral MRI changes. A similar case of Scleroderma 'en coup de
sabre' was published previously in JNNP. This case also had a brain biopsy
of a contralateral thalamic lesion and similar perivascular inflammatory
changes were seen [1].
Reports of neuropathology remain rare in these overlap conditions.
This additional report is useful in improving confidence in the hypothesis
that they are fundamentally neuroinflammatory disorders.
1. Stone J, Guthrie A, Franks A, Johnson MH. Scleroderma "en coup de
sabre": pathological evidence of intracerebral inflammation. Journal of
Neurology, Neurosurgery and Psychiatry 2001;70:382-385.
Dear Editor,
We agree that genetic studies have so far explained only a small fraction of the heritability of ALS (1,2), and this is true in many other diseases as well (3). Epigenetic factors are almost certainly part of the answer, but there are also several other possibilities. We are only just developing the tools to look for disease-associated rare variants on a large scale. In addition, we do not understa...
Dear Editor,
The twin studies show conclusively the limits of classical genetics in the studies of the etiology and pathogenesis of the ALS (1).
It has been suggested that a susceptibility or familial factor could play a role. In this case, they may be mediated by epigenetic mechanisms which control the activity and expression of the genome (2).
The incorrectly coded polypeptides could lead to...
Dear Editor,
The twin studies show conclusively the limits of classical genetics in the studies of the etiology and pathogenesis of the ALS (1).
It has been suggested that a susceptibility or familial factor could play a role. In this case, they may be mediated by epigenetic mechanisms which control the activity and expression of the genome (2).
The incorrectly coded polypeptides could lead to...
Dear Editor,
The article 'Disorders of Visual Perception' (ffytche, Blom & Catani, JNNP 2010;81:1280-1287) presents an interesting new classification of disorders of visual perception. It describes a wide range of disorders whose sources are cortical or subcortical rather than due to diseases of the eye. Each is classified as a disorder of one brain region (topological disorders) or of connectivity between re...
Recent developments by Harloff ( 2008 ) describibg high risk plaques detected by TOE and MRI in aortic arch , and cryptogenic stroke , depicted certain characteristics ( > 4 mm thickness or presence of ulcerations or mobile components ) . Considering associated conditions , such aortic thrombi are defined as laminated deposition along the initial surface with variable echogenicity with or without mobile lesions... Tou...
M.Tanaka Gutiez, L.Jarrett, B. Nevin, J. Stewart and S. Weatherby
Sir, A recent study published in the JNNP suggests that quality of life for people living with motor neuron disease (PwMND) is influenced by their perceptions of social support[1].
We would like to share the results of a study carried out jointly with the Motor Neurone Disease Association (MNDA) and the peninsula MND network, which fu...
I read the article by Weimar, et al with interest. The authors describe the largest case series to date of cervico-cephalic dissection in a multi-hospital registry in Germany. I found the findings on the risk of recurrent stroke being lower in the anti-coagulation group, similar in internal carotid versus vertebral artery, and higher in the occlusion versus stenosis group telling. The overall risk of recurrent stroke bein...
I read the article on disability progression in patients with multiple sclerosis whether treated with interferon or not with interest(1)
Although may of the placebo treated patients probably were treated with some form of immunomodulatory treatment after the study period, it certainly raises the question of whether neuronal progression in multiple sclerosis is due to accumulated deficits from exacerbations and re...
Moseley et al report an interesting case of Parry Romberg syndrome with contralateral MRI changes. A similar case of Scleroderma 'en coup de sabre' was published previously in JNNP. This case also had a brain biopsy of a contralateral thalamic lesion and similar perivascular inflammatory changes were seen [1].
Reports of neuropathology remain rare in these overlap conditions. This additional report is useful in...
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